Project description:RNA-sequencing of SSP RNA from patients with serrated polyposis syndrome identifies VSIG1 and MUC17 as potential diagnostic markers for SSPs 5' capped RNA from seven ascending SSPs, six patient matched uninvolved right colon and two normal right colon samples was used for RNA sequencing (15 samples total)
Project description:The immunodeficiency, centromere instability and facial anomalies (ICF) syndrome is associated with mutation of the DNA methyl-transferase DNMT3B, resulting in a reduction of enzyme activity. Aberrant expression of immune system genes and hypomethylation of pericentromeric regions accompanied by chromosomal instability were determined as alterations driving the disease phenotype. However, so far only technologies capable of analyzing single loci were applied to determine epigenetic alterations in ICF patients. In the current study, we performed whole-genome bisulphite sequencing to assess alteration in DNA methylation at base-pair resolution. Whole-genome bisulphite sequencing was performed to assess alteration in DNA methylation of one ICF patient and one healthy control sample at base-pair resolution.
Project description:We implicated the X-chromosome THOC2 gene, which encodes largest subunit of the highly-conserved TREX (Transcription-Export) complex, in a clinically variable neurodevelopmental disorder with intellectual disability as the core phenotype. To study how compromised function of this essential eukaryotic gene leads to NDD outcomes, we generated a clinically-relevant mouse model based on a hypomorphic Thoc2 exon 37-38 deletion variant of a patient with ID, speech delay, hypotonia, and microcephaly. The Thoc2 exon 37-38 deletion male (Thoc2/Y) mice recapitulate the core phenotypes of THOC2 syndrome including smaller size and weight, and significant deficits in spatial learning, working memory and sensorimotor functions. The Thoc2/Y mouse brain development is significantly impacted by compromised THOC2/TREX function resulting in R-loop accumulation, DNA damage and consequent cell death. Overall, we suggest that perturbed R-loop homeostasis, in stem cells and/or differentiated cells in mice and the patient, and DNA damage-associated functional alterations are at the root of THOC2 syndrome.